JPS6145609B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula The present invention relates to a gastric juice secretion suppressant containing a novel fused heterocyclic-S-oxide compound having the following formula and a pharmacologically acceptable acid addition salt thereof. In the above formula, R ¹ and R ² are the same or different and represent a hydrogen atom or a lower alkyl group, and X ¹
represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkanesulfonyl group, a halogen atom, a nitro group or a cyano group substituted at the 7th or 8th position, and n represents an integer of 1 to 2. In the preferred compound represented by the general formula (), R ¹ and R ² are the same or different and are hydrogen atoms or hydrogen atoms having 1 carbon number such as methyl, ethyl, n-propyl, isopropyl, n-butyl, and isobutyl.
It represents a linear or branched alkyl group having 4 to 4 alkyl groups, and X ¹ is a hydrogen atom, methyl, ethyl, n-propyl, isopropyl, n-butyl,
1 to 4 carbon atoms such as isobutyl and t-butyl
A straight or branched alkyl group having 1 to 4 carbon atoms; a straight or branched lower alkyl group having 1 to 4 carbon atoms such as methoxy, ethoxy, n-propoxy, isopropoxy, and n-butoxy Alkoxy group; linear or branched lower alkanesulfonyl group having 1 to 4 carbon atoms such as methanesulfonyl, ethanesulfonyl, propanesulfonyl, 1-methylethanesulfonyl, butanesulfonyl, 2-methylpropanesulfonyl ; a halogen atom such as fluorine, chlorine, bromine, and iodine; a nitro group; and a cyano group, and n is an integer of 1 or 2. Further, a condensed heterocyclic ring having the general formula () -
S-oxide compounds can be in the form of pharmacologically acceptable acid addition salts. Examples of pharmacologically acceptable acid addition salts include acid addition salts with inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, or with organic acids such as maleic acid and tartaric acid. As a result of various studies on fused heterocyclic-S-oxide compounds containing sulfur and nitrogen atoms, the present inventors found that a novel compound represented by the above general formula () is useful as a drug having an excellent gastric juice secretion suppressing effect. The present invention was completed based on the discovery that the compound is The pharmacological test and acute toxicity test results of the compound having the general formula () of the present invention are illustrated. The effect of suppressing gastric juice secretion is the Shay method [H.Shay:
Gastroen-terology, Vol . 5 , p. 43 (1945)], using shay rats.

【table】

【table】

[Table] Compound A: 1,3,4,6-tetrahydro-2H-5,1
-Benzothiazosine-S-oxide compound B: 1,3,4,6-tetrahydro-8-methyl-
2H-5.1-benzothiazocine-S-oxide compound C: 8-chloro-1.3.4.6-tetrahydro-
2H-5.1-Benzothiazocine-S-oxide Compound D: 1.3.4.6-tetrahydro-8-nitro-
2H-5.1-benzothiazocine-S-oxide compound E: 8-cyano-1.3.4.6-tetrahydro-
2H-5.1-benzothiazocine-S-oxide compound F: 8-bromo-1.3.4.6-tetrahydro-
6-Methyl-2H-5,1-benzothiazocine-
S-oxide compound G: 1.2.3.4.5.7-hexahydro-6.
1-Benzothiazonine-S-oxide compound H: 8-fluoro-1,3,4,6-tetrahydro-2H-5,1-benzothiazocine-S-oxide compound I: 1,3,4,6-tetrahydro-8- Methoxy-2H-5,1-benzothiazocine-S-oxide compound J: 7-chloro-1,3,4,6-tetrahydro-
2H-5.1-benzothiazocine-S-oxide compound K: 8-methanesulfonyl-1.3.4.6-tetrahydro-6-methyl-2H-5.1-benzothiazocine-S-oxide compound L: 8-methane Sulfonyl-1,3,4,6-tetrahydro-2H-5,1-benzothiazocine-S
-Oxide compound M: 7-chloro-1,3,4,6-tetrahydro-
2H-5.1-Benzothiazosine-S-oxide In order to use the compound having the above general formula () and its pharmacologically acceptable acid addition salt as a gastric juice secretion suppressant (anti-peptic ulcer agent), the dosage form thereof should be For example, tablets, capsules, granules, powders,
Oral administration such as syrup can be given. In preparing these formulations, excipients, binders, disintegrants, lubricants, flavoring agents, etc. may be added to the main drug according to conventional methods. The amount used varies depending on symptoms, age, weight, etc., but it is usually about 10mg per day for adults.
The dose ranges from 1,000 mg to 1,000 mg, and can be administered once or in divided doses. For parenteral administration, a single dose of 10 mg to 100 mg can be given by subcutaneous injection, intramuscular injection, or intravenous injection. Representative examples of compounds having the general formula () are listed below, but the compounds of the present invention are not limited thereby. (1) 1,3,4,6-tetrahydro-2H-5.
1-Benzothiazocine-S-oxide (2) 1,3,4,6-tetrahydro-8-methyl-2H-5,1-benzothiazocine-S-oxide (3) 8-fluoro-1,3,4,6- Tetrahydro-2H-5.1-benzothiazocine-S-oxide (4) 8-chloro-1.3.4.6-tetrahydro-2H-5.1-benzothiazocine-S-oxide (5) 8-bromo-1. 3,4,6-tetrahydro-6-methyl-2H-5,1-benzothiazocine-S-oxide (6) 7,8-dichloro-1,3,4,6-tetrahydro-2H-5,1-benzothiazocine- S
-Oxide (7) 8-bromo-10-chloro-1,3,4,6-
Tetrahydro-2H-5,1-benzothiazocine-S-oxide (8) 8-trifluoromethyl-1,3,4,6-
Tetrahydro-2H-5,1-benzothiazocine-S-oxide (9) 8-trifluoromethyl-1,3,4,6-
Tetrahydro-10-nitro-2H-5,1-benzothiazocine-S-oxide (10) 1,3,4,6-tetrahydro-8-nitro-2H-5,1-benzothiazocine-S-oxide (11) 8- Cyano-1,3,4,6-tetrahydro-2H-5,1-benzothiazocine-S-oxide (12) 1,3,4,6-tetrahydro-8-methoxy-2H-5,1-benzothiazocine-S- Oxide (13) 1, 2, 3, 4, 5, 7-hexahydro-
6,1-benzothiazonine-S-oxide The compound having the general formula () of the present invention has the general formula (In the formula, R ¹ , R ² , X ¹ and n have the same meanings as described above.) It can be obtained by oxidizing a fused ring heterocyclic compound. In carrying out this method, the reaction is accomplished by contacting a compound having the general formula () with an oxidizing agent. The solvent to be used is not particularly limited as long as it does not participate in this reaction, and alcohols such as methanol and ethanol are preferred. As an oxidizing agent, sodium periodate, t
-Organic peracids such as butyl hypochlorite, perbenzoic acid, m-chloroperbenzoic acid, hydrogen peroxide, N
- N-halogeno fatty acid imides such as chlorosuccinimide and iodosobenzene. The reaction proceeds satisfactorily at room temperature. The reaction time varies depending on the reaction temperature, but is usually 30 minutes to 5 hours. After completion of the reaction, the target compound of this reaction is collected according to a conventional method. The target compound thus obtained can be further purified, if necessary, by conventional methods such as recrystallization and column chromatography. The above general formula () used as a raw material compound
A compound having the general formula (In the formula, R ¹ , X ¹ and n have the same meanings as described above.) A ω-substituted thioalkylaniline derivative having the formula: formula (In the formula, Y represents a halogen atom, and R ¹ , X ¹ and n have the same meanings as described above.) by subjecting the new compound ( ) to a ring condensation reaction (second step). can get. The reaction in the first step can be carried out by bringing the ω-substituted thioalkylaniline derivative having the general formula () into contact with a halogen or an active halogen compound in an inert solvent. Active halogen compounds include N-halogeno fatty acid imides such as N-chlorosuccinimide and N-bromosuccinimide, alkaline earth metal hypochlorites such as calcium hypochlorite, and hypochlorite such as sodium hypochlorite. Mention may be made of N-halogenosulfonic acid amides such as alkali metal chlorates, tert-butylhypochlorite, chloramine T and dichloramine T. The inert solvent is not particularly limited, but aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, etc. are suitable. Although the reaction proceeds well below room temperature,
The reaction may be carried out at a temperature below the boiling point of the solvent. The reaction time varies depending on the reaction temperature, but is usually 5 minutes to 1 hour. The product having the general formula () is collected from the reaction mixture according to conventional methods. For example, it can be obtained by concentrating under reduced pressure after the completion of the reaction, but the reaction mixture can also be used as it is in the next reaction step. The reaction in the second step is a novel reaction achieved by bringing the compound having the general formula () into contact with a base in an inert solvent. Bases include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal alkoxides such as sodium methoxide and potassium ethoxide, trialkylamines such as triethylamine, and 1,5-diazabicyclo[5,4・
0] Organic bases such as undecene-5 are preferred. Suitable inert solvents include aliphatic halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride, water, and alcohols such as methanol and ethanol. The reaction proceeds satisfactorily even below room temperature, and a reaction temperature of 0-10°C is suitable. The reaction time varies depending on the reaction temperature, but is usually 2 minutes to 1 hour. Next, in the third step, which is carried out as necessary, the compound having the general formula () obtained in the second step, in which the substituent R ² is a hydrogen atom, is treated with an alkylating agent according to a conventional method. After contact or acylation, contact with a reducing agent to remove the substituents.
This is achieved by introducing a lower alkyl group as R ² . The alkylating agent is not particularly limited as long as it is used in ordinary alkylation, but examples include formic acid-formalin; alkyl halides such as methyl iodide, ethyl iodide, and isopropyl bromide; dimethyl sulfate and diethyl sulfate. Suitable examples include alkyl sulfates such as When using an alkyl halide or an alkyl sulfate, the reaction is preferably carried out in the presence of a base, and the bases used include sodium hydroxide,
alkali metal hydroxides, such as potassium hydroxide;
Examples include alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrides such as sodium hydride and potassium hydride, and alkali metal alkoxides such as sodium methoxide and sodium ethoxide. The acylating agent is not particularly limited as long as it is used in normal acylation, but examples include acyl halides such as acetyl chloride and propionyl chloride; acid anhydrides such as acetic anhydride and propionic anhydride. It can be cited as a suitable option.
The reaction is preferably carried out in the presence of a base, and the bases used include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, hydrogenated sodium, alkali metal hydrides such as potassium hydride, sodium methoxide,
Examples include alkali metal alkoxides such as sodium ethoxide. The reducing agent used in the reaction to reduce the acylated compound thus obtained is not particularly limited, but alkali metal aluminum hydrides such as lithium aluminum hydride and sodium aluminum hydride or diborane are suitable. be. The target compound having the general formula () obtained in the second and third steps is collected from the reaction mixture according to a conventional method. For example, after the reaction is completed, it is concentrated under reduced pressure and the residue is extracted with an organic solvent such as chloroform. The extract is washed with water and the solvent is distilled off under reduced pressure to obtain crystals, or if the obtained product is an oil, it is collected as a crystalline salt as described below. The target compound thus obtained can be further purified, if necessary, by conventional methods such as recrystallization, column chromatography, etc. Next, production examples, reference examples, and formulation examples of the compounds of the present invention will be given and explained. Production example 1 1,3,4,6-tetrahydro-2H-5,1
-Benzothiazocine-S-oxide 1,3,4,6-tetrahydro-2H-5,1
- 1.2 g of benzothiazocine was dissolved in 100 ml of methanol, and a solution of 1.2 g of sodium metaperiodate dissolved in 50 ml of water was added dropwise at room temperature, followed by stirring for 1 hour. The reaction mixture was poured into ice water and extracted with methylene chloride. The extract was concentrated under reduced pressure, and the residue was recrystallized from methanol to obtain 1.1 g of crystals with a melting point of 123-124°C. Elemental analysis value (%) C ₁₀ H ₁₃ Calculated value as NOS: C, 61.50; H, 6.71; N, 7.17; S, 16.41 Actual value: C, 61.34; H, 6.67: N, 7.05; S, 16.42 Production example 2 1,3,4,6-tetrahydro-8-methyl-
2H-5.1-Benzothiazocine-S-oxide 1.3.4.6-tetrahydro-8-methyl-
2.7 g of 2H-5.1-benzothiazocine was dissolved in 100 ml of methanol, and a solution of 3.5 g of sodium metaperiodate dissolved in 100 ml of water was added dropwise at room temperature, followed by stirring for 30 minutes. After the same treatment as in Production Example 1, recrystallization from methylene chloride-n-hexane resulted in 2.7 g of crystals with a melting point of 154-156°C (decomposition).
I got it. Elemental analysis value (%) Calculated value as C ₁₁ H ₁₅ NOS: C, 63.12; H, 7.22; N, 6.69; S, 15.31 Actual value: C, 62.82; H, 7.16; N, 6.60; S, 15.41 Production example 3 1,3,4,6-tetrahydro-8-methoxy-2H-5,1-benzothiazosine-S-oxide 2.2 g of 1,3,4,6-tetrahydro-8-methoxy-2H-5,1-benzothiazocine The mixture was dissolved in 100 ml of methanol, and a solution of 2.5 g of sodium metaperiodate dissolved in 100 ml of water was added dropwise at room temperature, followed by stirring for 1 hour. After the same treatment as in Production Example 1, the product was recrystallized from methylene chloride-benzene to obtain 1.8 g of crystals with a melting point of 155-157°C. Elemental analysis value (%) Calculated value as C ₁₁ H ₁₅ NO ₂ S: C, 58.63; H, 6.71; N, 6.21; S, 14.23 Actual value: C, 58.29; H, 6.54; N, 6.14; S, 14.16 Production example 4 8-fluoro-1,3,4,6-tetrahydro-2H-5,1-benzothiazosine-S-oxide 8-fluoro-1,3,4,6-tetrahydro-2H-5,1-benzothiazocine 3.7 g was dissolved in 100 ml of methanol, and a solution of 4 g of sodium metaperiodate dissolved in 100 ml of water was added dropwise at room temperature, followed by stirring for 30 minutes. After the same treatment as in Production Example 1, the product was recrystallized from methylene chloride-benzene to obtain 3.4 g of crystals with a melting point of 117-119°C. Elemental analysis value (%) C ₁₀ H ₁₂ Calculated value as FNOS: C, 56.31; H, 5.67; N, 6.56;
F, 8.90; S, 15.03 Actual value: C, 56.11; H, 5.54; N, 6.52;
F, 8.65; S, 14.70 Production example 5 8-chloro-1,3,4,6-tetrahydro-
2H-5.1-Benzothiazocine-S-oxide 8-chloro-1.3.4.6-tetrahydro-
Dissolve 8.4 g of 2H-5,1-benzothiazocine in 200 ml of methanol, dropwise add a solution of 10 g of sodium metaperiodate in 200 ml of water, and add 30 g of sodium metaperiodate to 200 ml of water.
Stir for minutes at room temperature. After treatment in the same manner as in Production Example 1, the product was recrystallized from methylene chloride-acetone to obtain 7.4 g of crystals with a melting point of 196-198°C (decomposition). Elemental analysis value (%) as C ₁₀ H ₁₂ ClNOS Calculated value: C, 52.28; H, 5.26; N, 6.09;
Cl, 15.43; S, 13.95 Actual value: C, 52.18; H, 5.49; N, 6.07;
Cl, 15.84; S, 14.15 Production example 6 1, 3, 4, 6-tetrahydro-8-nitro-
2H-5.1-benzothiazocine-S-oxide 1.3.4.6-tetrahydro-8-nitro-
2.2 g of 2H-5.1-benzothiazocine was dissolved in 200 ml of methanol, and a solution of 2 g of sodium metaperiodate in 200 ml of water was added dropwise thereto, followed by stirring at room temperature for 1 hour. After processing in the same manner as in Production Example 1, recrystallization from methanol was performed to obtain a melting point of
1.8 g of crystals at 233-235°C (decomposition) were obtained. Elemental analysis value (%) Calculated value as C ₁₀ H ₁₂ N ₂ O ₃ S: C, 49.98; H, 5.03; N, 11.65; S, 13.34 Actual value: C, 49.75; H, 5.00; N, 11.66; S , 13.55 Production example 7 8-cyano-1,3,4,6-tetrahydro-
2H-5.1-benzothiazocine-S-oxide 8-cyano-1.3.4.6-tetrahydro-
After dissolving 0.4 g of 2H-5,1-benzothiazocine in 50 ml of methanol, a solution of 0.5 g of sodium metaperiodate in 50 ml of water was added dropwise.
Stirred at room temperature for 1 hour. After processing in the same manner as in Production Example 1, recrystallization from methanol was performed, and the melting point was 234.
0.35 g of crystals at -236°C (decomposed) was obtained. Elemental analysis value (%) C ₁₁ H ₁₂ N ₂ Calculated value as OS: C, 59.97; H, 5.49; N, 12.71; S, 14.55 Actual value: C, 59.92; H, 5.33; N, 12.48; S, 14.63 Production example 8 8-bromo-1,3,4,6-tetrahydro-
6-Methyl-2H-5,1-benzothiazocine-S-oxide 8-bromo-1,3,4,6-tetrahydro-
6-Methyl-2H-5,1-benzothiazocine 2.2
g was dissolved in 100 ml of chloroform, 1.9 g of m-chloroperbenzoic acid was added thereto, and the mixture was stirred at room temperature for 2 hours. The reaction solution was washed with an aqueous sodium hydrogen carbonate solution, then washed with water and dried. This was concentrated under reduced pressure to obtain 2.1 g of the target compound as an oil. Mass spectrum m/e287 (M ⁺ )
(C ₁₁ H ₁₄ BrNOS), nuclear magnetic resonance spectrum (in deuterated chloroform) δ:
1.75 (doublet, 3H, CH ₃ ), 1.5−4.0 (multiplet, 6H, −(CH ₂ ) ₃ −), 4.80 (quartet, 0.4H, −
C HCH ₃ ), 4.88 (quartet, 0.6H, - C H+
_CH3 ), 6.9-7.6 (multiplet, 3H, H on benzene ring). Production example 9 1.2.3.4.5.7-hexahydro-6.
1-benzothiazonine-S-oxide 1.2.3.4.5.7-hexahydro-6.
Dissolve 1.5 g of 1-benzothiazonine in 100 ml of methanol, and add 2.0 g of sodium metaperiodate to this.
After dropping a solution of 50ml of water at room temperature, 1
Stir for hours. After processing in the same manner as in Production Example 1, the product was recrystallized from methylene chloride-benzene to obtain 1.2 g of crystals with a melting point of 130-132°C (decomposition). Elemental analysis value (%) Calculated value as C ₁₁ H ₁₅ NOS: C, 63.12; H, 7.22; N, 6.69; S, 15.31 Actual value: C, 63.02; H, 7.11; N, 6.64; S, 15.34 Production example 10 8-chloro-1,3,4,6-tetrahydro-
1-Methyl-2H-5,1-benzothiazocine-S-oxide 8-chloro-1,3,4,6-tetrahydro-
1-Methyl-2H-5・1-benzothiazocine 2.3
g was dissolved in 100 ml of methanol, and a solution of 2.6 g of sodium metaperiodate dissolved in 100 ml of water was added dropwise thereto, followed by stirring at room temperature for 30 minutes. Production example 1 below
After treatment in the same manner as above, recrystallization from isopropyl ether gave 1.5 g of crystals with a melting point of 89-91°C. Elemental analysis value (%) as C ₁₁ H ₁₄ ClNOS Calculated value: C, 54.20; H, 5.79; N, 5.75;
Cl, 14.54; S, 13.15 Actual value: C, 54.26; H, 5.78; N, 5.63;
Cl, 14.53; S, 13.31 Production example 11 1.3.4.6-tetrahydro-8-
Methanesulfonyl-2H-5,1-benzothiazocine-S-oxide 1,3,4,6-tetrahydro-8-methanesulfonyl-2H-5,1-benzothiazocine 2.7g
was dissolved in 100 ml of chloroform, 2.3 g of m-chloroperbenzoic acid was added thereto, and the mixture was stirred at room temperature for 2 hours. The reaction solution was washed with an aqueous sodium hydrogen carbonate solution, then washed with water and dried. Concentrate this under reduced pressure to crystallize
1.1g was obtained. Recrystallization from acetonitrile gave colorless crystals with a melting point of 215-216°C (decomposition). Elemental analysis value (%) Calculated value as C ₁₁ H ₁₅ NO ₃ S ₂ : C, 48.35; H, 5.49; N, 5.13; S, 23.44 Actual value: C, 48.42; H, 5.59; N, 5.26; S, 23.62 Production example 12 1,3,4,6-tetrahydro-8-methanesulfonyl-6-methyl-2H-5,1-benzothiazocine-S-oxide 1,3,4,6-tetrahydro-8-methanesulfonyl-6 -Methyl-2H-5,1-benzothiazocine 5.42g was added to methanol-water (250ml-100ml).
ml), and to this was added 5.0 g of fine powder of sodium metaperiodate crystals at room temperature, and the mixture was stirred for 3 hours. After methanol was distilled off under reduced pressure, the mixture was poured into ice water and extracted with methylene chloride. The extract was concentrated under reduced pressure and the residue was subjected to silica gel column chromatography (chloroform/ethyl ether/methanol: 4/2/
It was separated and purified in step 1). (±)-(6S・5R)-Compound Melting point 178-180℃
(Recrystallized from ethyl acetate-acetonitrile) Yield: 1.5 g. Elemental analysis value (%) Calculated value as C ₁₂ H ₁₇ NO ₃ S ₂ : C, 50.15; H, 5.96; N, 4.87; S, 22.31 Actual value: C, 50.17; H, 5.79; N, 4.73; S, 22.11 Nuclear magnetic resonance spectrum (in deuterium dimethyl sulfoxide) δ:

[Formula] 4.83 (quartet, J=7Hz) (C H ) 1.74 (double line, J=7Hz) (C H ₃ ) (±)-(6S・5S)-Compound Melting point 192-193℃
(Recrystallized from acetonitrile) Yield: 1.4 g. Elemental analysis value (%) Calculated value as C ₁₂ H ₁₇ NO ₃ S ₂ : C, 50.15; H, 5.96; N, 4.87; S, 22.31 Actual value: C, 50.11; H, 5.98; N, 4.79; S, 22.05 Nuclear magnetic resonance spectrum (in heavy dimethyl sulfoxide) δ:

[Formula] 4.85 (quartet, J=7Hz) (C H ) 1.60 (double line, J=7Hz) (C H ₃ ) Production example 13 7-chloro-1,3,4,6-tetrahydro-
2H-5・1-Benzothiazocine-S-oxide 7-chloro-1,3,4,6-tetrahydro-
2.5 g of 2H-5.1-benzothiazozine was dissolved in 50 ml of methanol, and a solution of 2.5 g of sodium metaperiodate dissolved in 50 ml of water was added dropwise at room temperature, followed by stirring for 1 hour. The reaction mixture was poured into ice water and extracted with methylene chloride. The extract was concentrated under reduced pressure, and the residue was recrystallized from methylene chloride-benzene to obtain crystals with a melting point of 165-168°C. Elemental analysis value (%) as C ₁₀ H ₁₂ ClNOS Calculated value: C, 52.28; H, 5.27; N, 6.10;
S, 13.96; Cl, 15.43 Actual value: C, 52.16; H, 5.31; N, 6.00;
S, 14.05; Cl, 15.63 Reference example 1 1.3.4.6-tetrahydro-2H-5.1
-Benzothiazosine Dissolve 2.7 g of N-chlorosuccinimide in 200 ml of chloroform, add 3.6 g of N-(3-methylthio)propylaniline at below 10°C, and stir for 5 minutes. The solvent was distilled off under reduced pressure to obtain 6.0 g of crystals of an equimolar mixture of 1-methyl-2-phenyl-isothiazolidinium chloride and succinimide. This product is a hygroscopic crystal that decomposes at 80℃. Nuclear magnetic resonance absorption spectrum (in deuterated chloroform)
δ: 2.9 (multiplet, 2H, -CH ₂ -), 3.30 (singlet, 3H, -S-CH ₃ ), 4.05 (multiplet, 2H, N
−CH ₂ −), 4.50 (triple line, J=7Hz, 2H, −S
−CH ₂ −), 7.0−7.5 (multiplet, 5H, phenyl ring hydrogen). Dissolve the above mixture in 100ml of chloroform,
4ml of 28% sodium methoxide-methanol solution
was added and stirred for 5 minutes. The reaction solution was washed with water, dried over sodium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (benzene) and then recrystallized from ether-n-hexane to obtain 3.2 g of crystals with a melting point of 77-79°C. Elemental analysis value (%) Calculated value as C ₁₀ H ₁₃ NS: C, 66.99; H, 7.31; N, 7.81; S, 17.88 Actual value: C, 66.89; H, 7.26; N, 7.54; S, 18.00 Formulation example 1 Oral capsule 6-methyl-8-methanesulfonylbenzothiazocine 100 mg Lactose 168.3 mg Corn starch 70 mg Magnesium stearate 1.7 mg Total 340 mg Mix the powders of the above formulation and pass through a 20-mesh sieve. After that, 340 mg of this powder was put into a No. 2 gelatin capsule to prepare a capsule.

Claims (1)

[Claims] 1. General formula (In the formula, R ¹ and R ² are the same or different and represent a hydrogen atom or a lower alkyl group, and X ¹ is a hydrogen atom, or a lower alkyl group substituted at the 7th or 8th position, a lower alkoxy group, or a lower alkanesulfonyl A gastric juice secretion suppressant containing a fused heterocyclic-S-oxide compound having a fused-ring heterocyclic-S-oxide compound, and an acid addition salt thereof.